L-ARGININE ATTENUATES PLATELET REACTIVITY IN HYPERCHOLESTEROLEMIC RABBITS

Platelets are capable of producing nitric oxide (NO) through the L-arg inine-NO synthase pathway. Acute exposure to supraphysiological concen trations of L-arginine in vitro increases the production of NO by plat elets and is associated with an increase in platelet cyclic GMP (cGMP) levels and a reduction in platelet aggregation. The purpose of this s tudy was to determine if chronic oral administration of L-arginine dec reases platelet aggregation in hypercholesterolemic animals and to det ermine if this effect is mediated by the metabolism of L-arginine to N O. Male New Zealand White rabbits were fed normal chow (Con), a 1% cho lesterol diet (Chol), or a 1% cholesterol diet supplemented with a six fold enrichment of dietary L-arginine (Arg) or L-methionine (Met). Aft er 10 weeks, cholesterol levels were equally increased in Chol and Arg animals, whereas plasma arginine levels were doubled in the Arg group . There was no difference in maximum aggregation initiated by ADP (100 mu mol/L) between washed platelets from Con, Met, and Chol animals, b ut aggregation of platelets from Arg animals was significantly decreas ed (P<.05). In aggregating platelets from Arg animals, cGMP levels wer e significantly higher than the other groups (P<.05). When platelets w ere incubated ex vivo with the NO synthase inhibitor N-G-monomethyl-L- arginine, the effects of dietary L-arginine were reversed. Chronic die tary supplementation of L-arginine decreases platelet aggregation in h ypercholesterolemic rabbits. This effect appears to be due to the meta bolism of L-arginine to NO.